Males and females are known to have distinct congitive capacities and emotional responses. Female rats acquire a classically conditioned eye blink response faster than male rats. Despite enhanced performance under unstressed conditions, females are severely impaired in acquiring the conditioned response by previous exposure to a stressful event, while males are facilitated. This grant proposes experiments to identify the neuronal, synaptic and molecular mechanisms responsible for 1) the facilitated learning in males versus the impaired learning in females after exposure to a stressful and emotional event, and 2) the enhanced performance of females under unstressed conditions. The proposed experiments will address the following questions. I) Is the stress induced impairment of learning in females dependent on estrogen and progesterone and an interaction with glucocorticoids? II) Is the amygdala necessary for the stress induced impairment of learning in females and their enhanced performance under unstressed conditions? III) Are stress induced effects on neuronal excitability in the amygdala associated with the sex differences in memory formation? IV) Are stress induced effects on spine/synaptic density in the amygdala associated with the sex differences in memory formation? V) Are the stress and sex effects on synaptic density and learning associated with the distribution of mRNA to dendritic spines in neurons of the amygdala? Methodologies will include behavioral training, transient lesioning and microinjections, multiple unit recording, Golgi impregnation and high resolution in situ hybridization. Females represent over 50 percent of the human population, yet they are vastly underrepresented in biomedical research. Despite the lack of attention, recent evidence suggests that estrogen is effective in the treatment of Alzheimer's disease, a devastating disease marked by abnormal cognitive and emotional responses and deterioration of the amygdala. The proposed experiments are clinically relevant because they address how estrogen contributes to the effective memory formation in the mammalian brain. In addition, they are relevant to post traumatic stress disorder (PTSD), a disease marked by the persistent behavioral and neuronal consequences of stressful experience.